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左乙拉西坦通过动脉自旋标记 MRI 测量可增加阿尔茨海默病患者海马区血流。

Levetiracetam Increases Hippocampal Blood Flow in Alzheimer's Disease as Measured by Arterial Spin Labelling MRI.

机构信息

Berenson-Allen Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Department of Neurology, Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark.

出版信息

J Alzheimers Dis. 2023;93(3):939-948. doi: 10.3233/JAD-220614.

DOI:10.3233/JAD-220614
PMID:37125545
Abstract

BACKGROUND

Patients with Alzheimer's disease (AD) have an increased risk of developing epileptiform discharges, which is associated with a more rapid rate of progression. This suggests that suppression of epileptiform activity could have clinical benefit in patients with AD.

OBJECTIVE

In the current study, we tested whether acute, intravenous administration of levetiracetam led to changes in brain perfusion as measured with arterial spin labeling MRI (ASL-MRI) in AD.

METHODS

We conducted a double-blind, within-subject crossover design study in which participants with mild AD (n = 9) received placebo, 2.5 mg/kg, and 7.5 mg/kg of LEV intravenously in a random order in three sessions. Afterwards, the participants underwent ASL-MRI.

RESULTS

Analysis of relative cerebral blood flow (rCBF) between 2.5 mg of levetiracetam and placebo showed significant decreases in a cluster that included the posterior cingulate cortex, the precuneus, and the posterior part of the cingulate gyrus, while increased cerebral blood flow was found in both temporal lobes involving the hippocampus.

CONCLUSION

Administration of 2.5 mg/kg of LEV in patients without any history of epilepsy leads to changes in rCBF in areas known to be affected in the early stages of AD. These areas may be the focus of the epileptiform activity. Larger studies are needed to confirm the current findings.

摘要

背景

阿尔茨海默病(AD)患者发生癫痫样放电的风险增加,这与疾病进展更快有关。这表明抑制癫痫样活动可能对 AD 患者具有临床益处。

目的

在目前的研究中,我们测试了急性静脉内给予左乙拉西坦是否会导致 AD 患者的脑灌注发生变化,这可以通过动脉自旋标记磁共振成像(ASL-MRI)来测量。

方法

我们进行了一项双盲、自身交叉设计研究,其中 9 名轻度 AD 患者以随机顺序在 3 个疗程中分别接受安慰剂、2.5mg/kg 和 7.5mg/kg 的 LEV 静脉内给药。之后,参与者接受了 ASL-MRI。

结果

与安慰剂相比,2.5mg 左乙拉西坦组的相对脑血流(rCBF)分析显示,在后扣带回皮质、楔前叶和扣带回后叶包括在内的一个簇中出现了显著的降低,而双侧颞叶包括海马区的脑血流增加。

结论

在没有癫痫病史的患者中给予 2.5mg/kg 的 LEV 会导致 rCBF 在 AD 早期受影响的区域发生变化。这些区域可能是癫痫样活动的焦点。需要更大的研究来证实目前的发现。

相似文献

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J Alzheimers Dis. 2023;93(3):939-948. doi: 10.3233/JAD-220614.
2
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引用本文的文献

1
Subclinical epileptiform discharges in Alzheimer's disease are associated with increased hippocampal blood flow.阿尔茨海默病中的亚临床癫痫样放电与海马血流增加有关。
Alzheimers Res Ther. 2024 Apr 12;16(1):80. doi: 10.1186/s13195-024-01432-9.
2
Epilepsy and epileptiform activity in late-onset Alzheimer disease: clinical and pathophysiological advances, gaps and conundrums.迟发性阿尔茨海默病中的癫痫和癫痫样活动:临床和病理生理学的进展、差距和难题。
Nat Rev Neurol. 2024 Mar;20(3):162-182. doi: 10.1038/s41582-024-00932-4. Epub 2024 Feb 14.
3
Disrupted Excitation-Inhibition Balance in Cognitively Normal Individuals at Risk of Alzheimer's Disease.
认知正常的阿尔茨海默病高危个体中兴奋-抑制平衡紊乱。
J Alzheimers Dis. 2023;95(4):1449-1467. doi: 10.3233/JAD-230035.
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Disrupted excitation-inhibition balance in cognitively normal individuals at risk of Alzheimer's disease.患阿尔茨海默病风险的认知正常个体的兴奋-抑制平衡失调。
bioRxiv. 2023 Aug 22:2023.08.21.554061. doi: 10.1101/2023.08.21.554061.